1. Field of the Invention
The present invention relates to the para-hydroxyalkylation of hydroxylated aromatic compounds, and, more especially, to the preparation of optionally substituted, p-hydroxymandelic compounds, more particularly the preparation of p-hydroxymandelic acid and 3-methoxy-p-hydroxymandelic acid.
By the term "hydroxylated aromatic compound," as utilized herein, is intended any aromatic compound bearing at least one hydroxyl substituent and the para-position of which being free or devoid of any substituents. By the term "optionally substituted, p-hydroxymandelic compound" is intended an aromatic compound at least bearing a --CHOH--COOH substituent in the para-position to a hydroxyl group.
2. Description of the Prior Art
One of the standard syntheses for the preparation of p-hydroxymandelic acids entails conducting a condensation, in an alkaline medium, of glyoxylic acid with phenol and/or its corresponding derivatives. The yield is limited by the fact that the condensation reaction is not selective and also produces o-hydroxymandelic acids and dimandelic acids.
In addition, the reaction yield is reduced as a result of a parasitic or competing secondary reaction. Thus, glyoxylic acid in an aqueous alkaline medium is transformed, via the Cannizaro reaction, into oxalic and glycolic acids. To prevent this Cannizaro reaction from preponderating and consuming the glyoxylic acid, FR-A-2,132,364 describes carrying out the condensation reaction in a diluted aqueous medium and at low or ambient temperature.
To improve the regio-selectivity of the reaction, EP-A-368,696 describes conducting the condensation of the glyoxylic acid with phenol in the presence of an amine. The amine is a tertiary amine which is liquid at ambient temperature and insoluble in water, such as, e.g., tributyl amine, trioctyl amine, triisooctyl amine or mixtures thereof. One of the disadvantages of this process is that the yields are not satisfactory, and range from 70% to 74%. Moreover, the phenol/glyoxylic acid molar ratio is very high, which mandates the recycling of a significant amount of phenol. Finally, another drawback to this process is that the reaction is carried out in a two-phase medium, requiring the separation of the aqueous and organic phases.